Multi-cartridge fluid delivery device

ABSTRACT

A fluid delivery device for administering a first medicament and a second medicament includes a first fluid reservoir configured to contain the first medicament and a second fluid reservoir configured to contain the second medicament. The fluid delivery device may include one or more basal drive mechanisms to provide a basal delivery of one or more of the first and second medicaments. The fluid delivery device may further include one or more bolus drive mechanisms to provide a bolus delivery of one or more of the first and second medicaments.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a U.S. national counterpart application under 35U.S.C. §371 of international application serial No. PCT/US2007/065363filed Mar. 28, 2007, which claims priority to U.S. Provisional PatentApplication No. 60/787,616 filed Mar. 30, 2006. The entire disclosuresof PCT/US2007/065363 and U.S. Ser. No. 60/787,616 are herebyincorporated by reference.

In addition, cross-reference is made to U.S. Pat. No. 6,939,324 titledFLUID DELIVERY AND MEASUREMENT SYSTEMS AND METHODS; U.S. PatentApplication Publication No. US 2005/0119618 titled HYDRAULICALLYACTUATED PUMP FOR LONG DURATION MEDICAMENT ADMINISTRATION; and U.S.application Ser. No. 11/219,944 titled FLUID DELIVERY AND MEASUREMENTSYSTEMS AND METHODS, the disclosure of each of which is herebyincorporated by reference herein.

FIELD OF THE DISCLOSURE

The present disclosure relates generally to fluid delivery devices andparticularly to fluid delivery devices capable of delivering one or moremedicaments to a patient to provide a sustained, basal delivery and/or abolus delivery of each medicament.

BACKGROUND

Fluid delivery devices, such as ambulatory infusion pumps, for example,have been developed for delivering liquid medicaments to a patient. Manysuch pumps or drug delivery devices are able to provide both steadystate delivery (“basal delivery”) and instantaneous bursts of apredetermined amount of drug (“bolus delivery”) as required. In manyinstances, it is beneficial to provide a basal delivery of a drug whichmay be supplemented by a bolus delivery as well. For example, insulinfor diabetes treatment as well as patient controlled analgesia forchronic pain treatment may be administered both at a continuous basalrate of delivery as well as via bolus amounts of delivery. Many suchdrug delivery devices are compact and able to be fixed to the user orpatient during use and subsequently disposed of when the treatment isfinished.

Many attempts have been made to provide continuous or near continuousbasal delivery of such medicaments using various pump systems. Theaccuracy of the basal delivery rate often varies when the volume of thedrug being delivered is small. Many fluid delivery devices include areservoir to contain the liquid medicament and use various mechanical,gas, or electromechanical pumping or metering technologies to deliverthe medicament to the patient via a needle or other catheter insertedtranscutaneously, or through the skin of the patient.

SUMMARY

The present invention comprises one or more of the features recited inthe appended claims or the following features or combinations thereof:

According to one aspect of the disclosure, a fluid delivery device foradministering a first medicament and a second medicament is provided.The fluid delivery device may function to administer a basal delivery ofthe first medicament and/or a basal delivery of the second medicament.Further, the fluid delivery device may function to administer a bolusdelivery of the first medicament and/or a bolus delivery of the secondmedicament. In other words, any combination of basal and/or bolusdeliveries of each of the first and second medicaments is contemplated.

Various configurations of basal drive mechanisms of the fluid deliverydevice may provide the basal delivery of the first and/or secondmedicament. For example, one basal drive mechanism may provide the basaldelivery of only the first medicament, only the second medicament, orboth the first and second medicaments. In instances where the basaldrive mechanism provides the basal delivery of only one of the first andsecond medicaments, a second basal drive mechanism of the fluid deliverydevice may provide the basal delivery of the other medicament.

Similarly, various configurations of bolus drive mechanisms of the fluiddelivery device may provide the bolus delivery of the first and/orsecond medicament. For example, one bolus drive mechanism may providethe bolus delivery of only the first medicament, only the secondmedicament, or both the first and second medicaments. In instances wherethe bolus drive mechanism provides the bolus delivery of only one of thefirst and second medicaments, a second bolus drive mechanism of thefluid delivery device may provide the bolus delivery of the othermedicament.

According to another aspect of the present disclosure, the fluiddelivery device may include one or more needles in fluid communicationwith the first and second reservoirs containing the first and secondmedicaments. For example, a first needle may be in fluid communicationwith the reservoir containing the first medicament while a second needlemay be in fluid communication with reservoir containing the secondmedicament. Such needles may be spaced-apart from each other orpositioned on opposite ends of the fluid delivery device tosubstantially prevent any mixing of the first and second medicamentsduring delivery. Further, one needle may include a delivery arm (forsubcutaneous insertion into the patient's skin) which is longer than adelivery arm of the other needle. In such a case, one of the first andsecond medicaments will be delivered to a subcutaneous depth greaterthan the other one of the first and second medicaments. Delivering themedicaments to a different depth may also substantially prevent anymixing of the first and second medicaments.

According to still another aspect of the present disclosure, a singleneedle may be provided which is in fluid communication with eachreservoir of the first and second medicaments. Such a needle may be“Y-shaped” and include a first uptake arm for fluid communication withthe reservoir containing first medicament and a second uptake arm forfluid communication with the reservoir containing the second medicament.Each of the first and second uptake arms of the needle may be in fluidcommunication with a delivery arm of the needle such that the first andsecond medicaments may mix with each other within the delivery arm ofthe needle prior to being delivered into the patient.

Illustratively, a fluid delivery device of the present disclosure mayinclude an exterior housing, a first reservoir within the housingconfigured to contain the first medicament, and a second reservoirwithin the housing configured to contain the second medicament. Thefluid delivery device may further include a needle having a first endconfigured for fluid communication with the first reservoir and a secondend configured to extend exteriorly from the housing. Alternatively, theneedle may include a third end configured for fluid communication withthe second reservoir containing the second medicament. The fluiddelivery device may further include a second needle having a first endconfigured for fluid communication with the second reservoir and asecond end configured to extend exteriorly from the housing. The firstneedle may be positioned at a first end of the housing while the secondneedle may be positioned at a second end of the housing. Further, adelivery arm of the first needle may be longer than a delivery arm ofthe second needle.

Further illustratively, the fluid delivery device may include a basaldrive mechanism for providing a basal delivery of the first medicament.The same basal drive mechanism may also provide a basal delivery of thesecond medicament. Alternatively, a second basal drive mechanism mayprovide the basal delivery of the second medicament. In either case, thebasal drive mechanism may include a coil spring, a basal drive piston,and a hydraulic fluid reservoir. Further, the fluid delivery device mayinclude a first pump chamber associated with the first medicament influid communication with the hydraulic fluid reservoir of the firstbasal drive mechanism via a first flow restrictor. Similarly, a secondpump chamber associated with the second medicament may be in fluidcommunication with the hydraulic fluid reservoir of the second basaldrive mechanism via a second flow restrictor.

Further illustratively, a first delivery piston of the fluid deliverydevice may be positioned within the first fluid reservoir to exert aforce on the first medicament within the first fluid reservoir.Similarly, a second delivery piston may be positioned within the secondfluid reservoir to exert a force on the second medicament within thesecond fluid reservoir.

The fluid delivery device may further include a bolus drive mechanismfor providing a bolus delivery of the first medicament. The same bolusdrive mechanism may also provide a bolus delivery of the secondmedicament. Alternatively, a second bolus drive mechanism may providethe bolus delivery of the second medicament. In either case, the bolusdrive mechanism may include a ratchet and a bolus piston coupled to theratchet. A pump chamber of the fluid delivery device is associated withthe first fluid reservoir and the bolus piston is positioned within abolus fluid reservoir in fluid communication with the pump chamber.

According to another aspect of the present disclosure, a method ofadministering first and second medicaments from an fluid delivery deviceincludes delivering a first basal delivery of the first medicament, anddelivering a second basal delivery of the second medicament. The firstbasal delivery may be approximately equal to the second basal delivery.Alternatively, the first basal delivery may be greater than the secondbasal delivery.

Illustratively, delivering the first medicament may include actuating afirst basal drive mechanism and delivering the second medicament maysimilarly include actuating the first basal drive mechanism.Alternatively, delivering the second medicament may include actuating asecond basal drive mechanism different from the first basal drivemechanism.

The method may further include delivering a first bolus delivery of thefirst medicament and delivering a second bolus delivery of the secondmedicament. The first bolus delivery may be the same as the second bolusdelivery. Alternatively, the first bolus delivery may be greater thanthe second bolus delivery.

Illustratively, delivering the first bolus delivery may includeactuating a first bolus drive mechanism and delivering the second bolusdelivery may include actuating the first bolus drive mechanism.Alternatively, delivering the second bolus delivery may includeactuating a second bolus drive mechanism different from the first bolusdrive mechanism.

According to still another aspect of the present disclosure, anothermethod of administering first and second medicaments from a fluiddelivery device includes (i) forcing hydraulic fluid from a hydraulicfluid reservoir into a first pump chamber to exert a force on a firstmovable barrier, (ii) forcing hydraulic fluid from the hydraulic fluidreservoir into a second pump chamber to exert a force on a secondmovable barrier, (iii) exerting a force on a first piston to expel atleast a portion of the first medicament through an aperture of the firstfluid reservoir, and (iv) exerting a force on a second piston to expelat least a portion of the second medicament through an aperture of thesecond fluid reservoir.

Illustratively, forcing the hydraulic fluid from the hydraulic fluidreservoir may include applying a spring force to a piston within thehydraulic fluid reservoir. Forcing the hydraulic fluid from thehydraulic fluid reservoir may further include forcing hydraulic fluidfrom the hydraulic fluid reservoir through a flow restrictor and intothe first and second pump chambers.

The fluid delivery devices described herein may be used to delivery awide variety of drugs, pharmaceutical agents, and medicaments, and othercomponents useful for treating diseases and disease states. In oneembodiment, the delivery devices described herein include or areconfigured or adapted to include pre-selected medicaments in thecorresponding reservoirs. In one aspect, the pre-selected medicamentsare used to treat diabetes and/or diabetic conditions. In anotheraspect, the pre-selected medicaments are used to treat bacterialinfections and/or other diseases associated with pathogenic cellpopulations. In another aspect, the pre-selected medicaments are used totreat diseases associated with neurotransmitter dysfunction, includingbut not limited to diseases that are treatable with dopamine and/orcompounds that function as dopamine agonists and/or dopamineantagonists.

The above and other features of the present disclosure will becomeapparent from the following description and the attached drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The detailed description particularly refers to the accompanying figuresin which:

FIGS. 1-5 b are schematics showing dual-cartridge drug delivery devicesof the present disclosure which provide a basal delivery of both firstand second medicaments and which provide a bolus delivery of both firstand second medicaments;

FIGS. 6-7 are schematics showing additional drug delivery devices of thepresent disclosure which provide a basal delivery of the firstmedicament only and a bolus delivery of the first and secondmedicaments;

FIGS. 8-9 are schematics further showing additional drug deliverydevices of the present disclosure which provide a basal delivery of thefirst and second medicaments while providing a bolus delivery of onlythe second medicament;

FIGS. 10-11 are schematics showing further drug delivery devices of thepresent disclosure which provide a basal delivery of the first andsecond medicaments while providing no bolus delivery for either of thefirst or second medicaments;

FIGS. 12-13 are schematics showing additional drug delivery devices ofthe present disclosure which provide a bolus delivery of the first andsecond medicaments while providing no basal delivery for either of thefirst or second medicaments;

FIG. 14 is a schematic of another drug delivery device of the presentdisclosure which provides a bolus delivery of only the first medicamentand a basal delivery of only the second medicament;

FIG. 15 is a schematic of another drug delivery device of the presentdisclosure which provides a balloon-like basal fluid reservoirassociated with each of the first and second medicaments and analternative basal drive mechanism coupled to the respective basal fluidreservoirs;

FIG. 16 is a schematic of another drug delivery device of the presentdisclosure similar to the device shown in FIG. 15 and providing a singlealternative basal drive mechanism and balloon-like basal fluid reservoirfor providing a basal delivery of each of the first and secondmedicaments;

FIG. 17 is a schematic of another drug delivery device of the presentdisclosure similar to the device shown in FIG. 1 where a delivery pistonassociated with each of the first and second medicaments of FIG. 1 issubstituted with a flexible member;

FIG. 18 is a schematic of a needle configuration of the presentdisclosure including first and second needles having delivery arms ofdifferent lengths to deliver the first and second medicaments at adifferent subcutaneous depth within the patient; and

FIG. 19 is a schematic of a generally “Y-shaped” needle for fluidcommunication with the reservoir of each of the first and secondmedicaments.

DETAILED DESCRIPTION OF THE DRAWINGS

Looking first to FIGS. 1-5 b, various fluid or drug delivery devices 10,110, 210, 310, 410, and 450 are provided. Each of these drug deliverydevices 10, 110, 210, 310, 410, and 450 is capable of delivering a firstmedicament 20 at both a sustained steady state or basal delivery orinfusion as well as an instantaneous amount of the first medicament 20to provide a short term pulsatile or bolus delivery or infusion.Further, each of the drug delivery devices 10, 110, 210, 310, 410, and450 is able to provide both a basal delivery of a second medicament 22and a bolus delivery of the second medicament 22. The means by whicheach device delivers the first and second medicaments is discussedbelow.

It should be appreciated that the fluid delivery devices describedherein each include an outer or exterior housing (not shown). Thestructures shown in FIGS. 1-17, therefore, are generally containedwithin such a housing. Illustratively, the housing may include variousbuttons or actuators engagable by a user or patient which activate thebasal and bolus drive mechanisms described herein. Further, as isdiscussed in greater detail below, the needles 32, 34 of each fluiddelivery device shown in FIGS. 1-17 are movable between a first,un-activated configuration (not shown) whereby the entirety of theneedle is either contained within the outer housing and/or within anexternal button of the outer housing, and a second activatedconfiguration. In the second activated configuration (shown in FIGS.1-17), the needle is lowered such that one portion of the needle is influid communication with a reservoir containing one of the first andsecond medicaments 20, 22 and a second portion of the needle ispositioned outside of the outer housing of the device for subcutaneousinsertion into a patient, for example. Illustratively, the needle isconfigured for generally simultaneous insertion into one of the fluidreservoirs (or the stopper associated with each reservoir) and thepatient. In other words, movement of the needle from the un-activatedposition to the activated position will generally simultaneously placethe first end of the needle into fluid communication with the associatedfluid reservoir while placing the second end of the needle into thepatient.

Looking now to FIG. 1, the drug delivery device 10 includes a first drugreservoir or cartridge 12 and a second drug reservoir or cartridge 14.As such, the drug delivery device 10 (as well as other drug deliverydevices described herein) may be considered a dual-cartridge device.Illustratively, the first medicament 20 is contained within the firstreservoir 12 while the second medicament 22 is contained within thesecond reservoir 14. A first septum or stopper 24 is received in partwithin the inner chamber of the first reservoir 12 such that a portionof the first stopper 24 protrudes from a proximal end 25 of the firstreservoir 12. The first stopper 24 includes a hollow chamber 26 in fluidcommunication with the first reservoir 12. Similarly, a second stopper28 is received in part within the inner chamber of the second reservoir14 such that a portion of the second stopper 28 protrudes from theproximal end 25 of the second reservoir 14. The second stopper 28similarly includes the hollow chamber 26 in fluid communication with thesecond reservoir 14. Illustratively, the first and second stoppers 24,28 may each be made from rubber. It is within the scope of thisdisclosure, however, for the first and second stoppers 24, 28 to be madefrom other suitable materials as well.

First and second needles 32, 34 of the drug delivery device 10 eachinclude a first end 36 and a second end 38. The first end 36 of eachneedle 32, 34 is received through an outer wall of the respective firstand second stoppers 24, 28 for positioning within the hollow chamber 26of each stopper 24, 28. The second end 38 of each needle 32, 34 isprovided for subcutaneous insertion into a patient in order to deliverthe first and second medicaments 20, 22 to the patient. Illustratively,the first and second needles 32, 34 are shown to define a “J-shape” suchthat each needle 32, 34 includes an uptake arm 40 and a delivery arm 42which are generally parallel to each other and a transverse arm 44connecting the uptake and delivery arms 40, 42 together. Each arm 40,42, 44 of each needle 32, 34 is cannulated to provide a generallycontinuous J-shaped passageway to allow the respective first and secondmedicaments 20, 22 to travel from the first end 36 of each needle 32, 34to the second end 38 of each needle 32, 34.

As shown in FIG. 1, the arms 40, 42 of each needle 32, 34 have differentlengths. It is within the scope of this disclosure, however, to includeneedles 32, 34 having arms 40, 42, 44 of varying or same lengths. It isalso within the scope of this disclosure to include other needle designswhere one end of the needle is positioned or able to be positionedwithin the hollow chamber 26 of one of the stoppers 24, 28 and where theother end of the needle is able to be subcutaneously inserted into apatient. Further, it is within the scope of this disclosure to includeother infusion devices for delivering the medicaments 20, 22 from theirrespective reservoirs 12, 14 to the patient. For example, a lumen and aneedle set, a catheter-cannula set, and/or a microneedle or microneedlearray attached by one or more lumens may be used in place of the needles32, 34. Further each of the fluid reservoirs 12, 14 may include anaperture through which the medicaments 20, 22 within each chamber areexpelled. One of ordinary skill in the art will appreciate that manydevices may be used to convey medicaments into a body. Accordingly, thepresent disclosure is not limited to the types of infusion or injectiondevices shown herein.

Looking again to FIG. 1, the drug delivery device 10 includes a firstbasal drive mechanism 46 which provides a basal delivery of the firstmedicament 20 to the patient. The first basal drive mechanism 46includes a coil spring 48 secured to a basal drive piston 50. The basaldrive piston 50 is positioned in the inner chamber of a basal fluidreservoir 52. The basal drive piston 50 is movable relative to the wallsof the fluid reservoir 52. A pump chamber 54 is in fluid communicationwith the basal fluid reservoir 52 through a connective passageway orflow restrictor 56. The spring 48 exerts a generally constant force ontothe basal drive piston 50 to assert pressure on the hydraulic fluidwithin the basal fluid chamber 52.

A driven or delivery piston 58 of the drug delivery device 10 ispositioned within the inner chamber of the reservoir 12 and operates asa partition or movable barrier between the first medicament 20 containedwithin the first drug reservoir 12 and the hydraulic fluid containedwithin the pump chamber 56. Illustratively, the hydraulic fluidcontained within the pump chamber 54 and the basal fluid reservoir 52 isan oil (not shown), or particularly a silicone oil, for example.However, these chambers may be filled with other non-compressible fluidsas well such as those disclosed in U.S. Patent Application PublicationUS 2005/0119618, the disclosure of which is hereby incorporated byreference herein.

In operation, the coil spring 48 of the first basal drive mechanism 46slowly expands to exert a bias on the basal drive piston 50 therebyexerting a force on the hydraulic fluid within the basal fluid reservoir52 and the pump chamber 54. Such an increase in fluid pressure withinthe pump chamber 54 urges the delivery piston 58 to the right (as viewedin the orientation of FIG. 1). Such movement of the piston 50 causes aquantity of the first medicament 20 within the reservoir 12 to be forcedthrough the needle 32 and delivered to a patient. The operation of sucha basal drive mechanism is discussed in greater detail within U.S.Patent Application Publication No. US 2005/0119618.

The drug delivery device 10 further includes a second basal drivemechanism 60 which provides a basal delivery of the second medicament 22to the patient. The second basal drive mechanism 60 is the same as orsimilar to the first basal drive mechanism 46. As such, like referencenumerals have been used to denote like components. For example, thesecond basal drive mechanism 60 includes the coil spring 48 secured tothe basal drive piston 50. The basal fluid reservoir 52 of the secondbasal system is in fluid communication with the pump chamber 54 throughthe connective passageway or flow restrictor 56. Similarly, the fluidreservoir 52, pump reservoir 54, and flow restrictor 56 associated withthe second medicament are each filled with an oil such as a siliconeoil, for example. Further, the second basal drive mechanism 60 operatesthe same as or similarly to the first basal drive mechanism 46 to forcethe second medicament 22 from within the second reservoir 14 through theneedle 34 and into a patient.

As discussed above, the fluid delivery device 10 includes two separatebasal drive mechanisms 46, 60 to provide a basal delivery of each of thefirst and second medicaments 20, 22. In operation, a single button oractuator may be activated by a user to actuate both of the first andsecond drive mechanisms 46, 60 at one time. Of course, separateactuators may be used to independently actuate each of the drivemechanisms 46, 60 as well. Illustratively, such button(s) or actuator(s)may be located on or within the outer housing (not shown) of the fluiddelivery device 10 to be activated by a user or patient.

Looking still to FIG. 1, a single bolus drive mechanism 62 is used toprovide a bolus delivery of each of the first and second medicaments 20,22. The bolus drive mechanism 62 includes a ratchet 64 having a toothedrack 66 and a pawl 68 engaged with the teeth of the toothed rack 66. Thetoothed rack 66 is coupled to a dual-head piston assembly 70 includingfirst and second arms 72, 74 spaced-apart from each other by atransverse arm 76 coupled to both the first and second arms 72, 74.Illustratively, the toothed rack 66 of the ratchet 64 is coupled to thetransverse arm 76. A bolus drive piston 78 is coupled to each of thefirst and second arms 72, 74 of the dual-head piston assembly 70. Eachof the pistons 78 is positioned within an interior chamber of one or apair of bolus delivery reservoirs 80. The bolus delivery reservoirs 80are in fluid communication with their respective pump chambers 54.

In operation, a force applied to the toothed rack 66 advances thedual-head piston assembly 70 to force fluid from each bolus fluidreservoir 80 into the respective pump chamber 54 to move the respectivedriven piston 58 thereby causing bolus delivery of both the first andsecond medicaments 20, 22 from the respective first and second drugreservoirs 12, 14. A bolus actuator button may be coupled to the toothedrack 66 such that when a user depresses the bolus actuator button, thetoothed rack 66 is advanced a pre-determined distance. Alternatively,such a bolus actuator button may be coupled to the pawl 68 such thatwhen a user depresses the bolus actuator button, the pawl 68 is advanceda predetermined distance and forces the toothed rack 66 to advance thesame predetermined distance as well. With such an arrangement, asecondary mechanism may be used to retract the pawl 68 relative to thetoothed rack 66 to an activated position such that the pawl 68 may beadvanced again to provide another bolus delivery. In either case, thepawl 68 of the ratchet 64 prevents the toothed rack 66 from movingbackward after having been advanced. Further, the pawl 68 of the ratchet64 prevents the toothed rack 66 from moving backward due to anyincreased fluid pressure caused by fluid moving from the basal fluidreservoirs 52 into the pump chambers 54, for example.

As described above, the fluid delivery device 10 includes two separatefluid reservoirs 12, 14 containing two different medicaments 20, 22therein. Illustratively, separate needles 32, 34 are provided to delivereach medicament 20, 22 to a patient. However, it is within the scope ofthis disclosure to include a single needle for delivering each of thefirst and second medicaments 20, 22. Such embodiments are discussed ingreater detail below.

Looking now to FIG. 2, a fluid delivery device 110 is similar to thefluid delivery device 10 described above. As such, the same referencenumerals have been used to denote the same or similar components. Thefluid delivery device 110 includes a first bolus piston 178 positionedwithin a first bolus reservoir 180. The bolus piston 178 is larger thanthe bolus piston 78. Specifically, the first bolus piston 178 has adiameter D1 that is greater than the diameter D2 of the second boluspiston 78. As such, the bolus piston 178 has a greater surface area thanthe second bolus piston 78. The disparity in size between the first andsecond bolus pistons 78, 178 produces a different bolus delivery (e.g.quantity or amount of medicament being delivered) of each of the firstand second medicaments 20, 22 in response to movement of the dual headpiston assembly 70.

In other words, the concerted movement of the pistons 78, 178 operatesto displace a different amount of fluid from the respective bolusreservoirs 80, 180 to act on the driven piston 58 associated with eachof the first and second reservoirs 12, 14. This causes a greaterpressure to be exerted on the piston 58 associated with the reservoir 12relative to the pressure associated with the reservoir 14. This in turncauses a larger bolus delivery of the first medicament 20 to bedelivered relative to the bolus delivery of the second medicament 22.Therefore, an incremental movement of the dual-head piston assembly 70of the bolus drive mechanism 62 will cause a greater amount of the firstmedicament 20 to be delivered to the patient than the second medicament22.

In many instances, for example, it may be preferable to deliver a firstamount of a first medicament with a second amount of a secondmedicament. Varying the size of the bolus drive piston, therefore,allows the ratio of the two medicaments delivered in a bolus delivery tobe varied. In other words, it is within the scope of this disclosure tovary the size of the bolus pistons of the fluid delivery devicesdescribed herein in order to achieve any desired bolus delivery ratiobetween the two medicaments being delivered to a patient.

As is discussed in greater detail below, the size of other componentsassociated with the fluid delivery device (e.g., drive pistons, flowrestrictors, etc.) may also be varied in order to basally deliver thefirst medicament at a different rate than the second medicament. Again,any of these dimensions may be configured in order to produce a desiredratio between the basal delivery rates of the first and secondmedicaments.

Looking now to FIG. 3, another fluid delivery device 210 is provided.Again, the fluid delivery device 210 is similar to devices 10, 110described above. As such, like reference numerals have been used todenote like components. The fluid delivery device 210 includes a firstbolus drive mechanism 280 and a second bolus drive mechanism 282. Eachof the first and second bolus drive mechanisms 280, 282 includes aratchet 64 having a toothed rack 66 and a pawl 68 engaged with the teethof the toothed rack 66. Each bolus drive mechanism 280, 282 furtherincludes a piston 78 coupled to one end of each toothed rack 66 andpositioned within an inner chamber of the respective bolus fluidreservoirs 80. As such, the bolus delivery feature of each medicament20, 22 is operated independently by separate bolus drive mechanisms 280,282.

In operation, the bolus drive mechanisms 280, 282 may, therefore, beactuated independently to separately advance each of the toothed racks66 of the separate bolus drive mechanisms 280, 282 enabling a user toprovide one bolus delivery of one of the medicaments 20, 22 withoutproviding a bolus delivery of the other medicament 20, 22. For example,actuation by a user of the first bolus drive mechanism 280 provides abolus delivery of only the first medicament 20 while actuation of thesecond bolus drive mechanism 282 provides a bolus delivery of only thesecond medicament 22. Of course, the bolus drive mechanisms 280, 282 mayalso be actuated by a single actuator (not shown) which is able toadvance each of the toothed racks 186 at the same time.

Looking now to FIG. 4, the fluid delivery device 310 is provided. Thedelivery device 310 is similar to the delivery devices 10, 110, and 210described above. As such, like reference numerals have been used todenote like components. The fluid delivery device 310 includes a singlebasal drive mechanism 346 having the coiled spring 48 and the basaldrive piston 50. A basal fluid reservoir 352 is in fluid communicationwith both the respective pump chambers 54 associated with each of thefirst and second drug reservoirs 12, 14. Illustratively, a first flowrestrictor 356 is positioned between the fluid reservoir 352 and thepump chamber 54 associated with the first reservoir 12. A second flowrestrictor 358 is positioned between the fluid reservoir 352 and thepump chamber 54 associated with the second reservoir 14. Illustratively,the first flow restrictor 356 is positioned upstream of the second flowrestrictor 358. It is within the scope of this disclosure, however, toprovide a similar fluid delivery device wherein the flow restrictorassociated with the second medicament is positioned upstream from theflow restrictor associated with the first medicament or alternativelywhere the two flow restrictors are in parallel with each other. In otherwords, the position or location of the flow restrictor associated witheach of the first and second basal drive mechanisms may be altered asdesired.

The single basal drive mechanism 346 of the fluid delivery device 310drives the basal delivery for both the first and second medicaments 20,22. Thus, actuation of the drive mechanism 346 to permit the coil spring48 to advance the basal drive piston 50 will cause both of the drivenpistons 58 to advance as well. Illustratively, the size (includingdiameter, or width, and length) of each of the flow restrictors 356,358, the pump chambers 54, the pistons 58, and the drug reservoirs 12,14 are shown to be generally the same. As such, the rate of basaldelivery of the first and second medicaments 20, 22 will generally bethe same or similar. However, it should be appreciated that varying oneor more of the dimensions of one or more of the aforementionedcomponents associated with either medicament 20, 22 will provide a fluiddelivery device which is capable of delivering the first medicament 20at a first basal delivery rate while the second medicament 22 isdelivered at a second basal delivery rate different from the first basaldelivery rate. In such a scenario, these differing basal delivery ratesare provided with the use of a single basal drive mechanism.

According to another aspect of the present disclosure, a fluid deliverydevice (not shown) similar to the fluid delivery device 310 of FIG. 4may similarly include a single basal drive mechanism for providing abasal delivery of each of the first and second medicaments 20, 22.However, such a fluid delivery device may include a basal fluidreservoir in communication with a single pump chamber via a single flowrestrictor. A tail end of a generally Y-shaped piston (not shown) may bereceived within the single pump chamber while each spaced-apart arm ofthe Y-shaped piston may be received within the fluid reservoir 12, 14containing the respective medicaments 20, 22.

As such, the drive mechanism operates to expel hydraulic fluid, such assilicone oil, for example, from the basal fluid reservoir, through theflow restrictor, and into the pump chamber to act upon the tail end ofthe Y-shaped piston. This force on the Y-shaped piston causes the pistonto thereby expel the first and second medicaments 20, 22 from thereservoirs 12, 14. In such a fluid delivery system, a single bolus drivemechanism may also actuate bolus delivery of each of the first andsecond medicaments. Further, piston arms having a different size ordifferent cross-sectional surface area relative to one another providesfor a different basal delivery and a different bolus delivery betweenthe two medicaments 20, 22.

Illustratively, the fluid delivery device 310 shown in FIG. 4 includesthe single bolus drive mechanism 62 similar to that shown in FIGS. 1 and2 for providing bolus delivery of both the first and second medicaments20, 22. However, a fluid delivery device, such as the fluid deliverydevice 410 shown in FIG. 5 a, may be provided which includes the singlebasal drive mechanism 346 shown in FIG. 4 and separate bolus drivemechanisms 280, 282 similar to those shown in FIG. 3.

Further, a fluid delivery device 450, shown in FIG. 5 b, is similar tothe fluid delivery device 410 shown in FIG. 5 a. For example, the device450 similarly includes a single basal drive mechanism 346 and provides abasal delivery of each of the first and second medicaments 20, 22 whiletwo separate bolus drive mechanisms 280, 282 provide a bolus delivery ofeach of the first and second medicaments 20, 22. Illustratively,however, two flow restrictors 356, 357 fluidly connect the basal fluidreservoir 352 with the pump chamber 54 associated with the firstreservoir 12. A single flow restrictor 358 is provided between the basalfluid reservoir 352 and the pump chamber 54 associated with the secondreservoir 14. The dual flow restrictors 356, 357 allow additionalhydraulic fluid (not shown) from the basal fluid reservoir 352 to enterthe pump chamber 54 associated with the first reservoir 12. As such, agreater pressure is exerted on the drive piston 58 associated with thefirst reservoir 12 than that which is exerted on the drive piston 58associated with the second reservoir 14. This in turn causes a largerbasal delivery (i.e., a greater rate of delivery) of the firstmedicament 20 to be delivered relative to the basal delivery of thesecond medicament 22. Other systems may be provided including any numberof flow restrictors connecting the fluid reservoir 352 with either oneof the pump chambers 54.

As discussed above, each of the fluid delivery devices 10, 110, 210,310, 410, and 450 are able to provide both a basal delivery and a bolusdelivery of the first medicament 20 as well as both a basal delivery anda bolus delivery of the second medicament 22. This function may beaccomplished through various combinations of various features of thesedevices 10, 110, 210, 310, 410, and 450. For example, the fluid deliverydevice 10 includes two separate basal drive mechanisms and a singlebolus drive mechanism able to provide a bolus delivery of each of thefirst and second medicaments 20, 22. The fluid delivery device 210 ofFIG. 3, on the other hand, includes two separate basal drive mechanismsand two separate bolus drive mechanisms. The fluid delivery device 310of FIG. 4 includes only one basal delivery mechanism and one bolusdelivery mechanism while the fluid delivery devices of FIGS. 5 a and 5 binclude a single basal delivery mechanism and two separate bolusdelivery mechanisms.

As noted above, the fluid delivery device 110 of FIG. 2 illustrates asize difference between the surface area of the bolus drive pistons 178,78 associated with each of the first and second reservoirs 12, 13 inorder to provide a different bolus delivery of each of the first andsecond medicaments 20, 22 using the single bolus drive mechanism 62. Aswas mentioned previously, the dimension(s) of many other components ofthe various fluid delivery devices 10, 110, 210, 310, 410 and 450 may bevaried in order to provide a device wherein the basal and/or bolusdeliveries of the first and second medicaments 20, 22 are different fromeach other.

Looking now to FIGS. 6 and 7, fluid delivery devices 510 and 610 areprovided. The fluid delivery devices 510, 610 are similar in nature tothe fluid delivery devices described above in FIGS. 1-5 b. As such, likereference numerals have been used to denote like components. Each of thefluid delivery devices 510 and 610 provides a basal delivery of only onemedicament, illustratively, the first medicament 20. In other words,neither of the fluid delivery devices 510, 610 shown in FIGS. 6 and 7provides a basal delivery of the second medicament 22. However, a bolusdelivery of each medicament 20, 22 is provided. This arrangement may bebeneficial for the use of various combinations of first and secondmedicaments where a basal delivery is necessary for only one medicament,but where a bolus delivery of each medicament is desired. Of course, thefluid delivery devices 510, 610 may instead be configured to provide abasal delivery of only the second medicament 22.

Looking first to FIG. 6, the fluid delivery device 510 includes onebasal drive mechanism 46 for providing a basal delivery of the firstmedicament 20. The fluid delivery device 510 further includes one bolusdrive mechanism 62 for providing a bolus delivery of each of the firstand the second medicaments 20, 22. The fluid delivery device 610 of FIG.7 includes one basal drive mechanism 46 for providing a basal deliveryof the first medicament 20. The fluid delivery device 610 furtherincludes the first bolus drive mechanism 280 for providing a bolusdelivery of the first medicament 20 and the second bolus drive mechanism282 for providing a bolus delivery of the second medicament 22. Ofcourse, the dimension(s) of many of the components of the fluid deliverydevices 510, 610 may be varied in order to provide a device wherein thebolus delivery of the first and second medicaments 20, 22 are differentfrom each other.

Looking now to FIGS. 8 and 9, fluid delivery devices 710 and 810 areprovided. Each of these fluid delivery devices 710, 810 are similar tothe fluid delivery devices described above. As such, like referencenumerals are used to denote like components. The fluid delivery devices710, 810 shown in FIGS. 8 and 9 each provide a basal delivery of thefirst and second medicaments 20, 22 while providing a bolus delivery ofonly the second medicament 22. No bolus delivery function is providedfor the first medicament 20. Of course, the fluid delivery devices 710,810 may be modified to provide a bolus delivery of the first medicament20 only. Such an arrangement may be beneficial where it is desired tobasally deliver two different medicaments to a patient while providing abolus delivery of only one of the two medicaments.

Looking first to FIG. 8, the fluid delivery device 710 includes thefirst basal drive mechanism 46 to provide basal delivery of the firstmedicament 20 and the second basal drive mechanism 60 to provide basaldelivery of the second medicament 22. The single bolus deliverymechanism 282 provides the bolus delivery of the second medicament 22.Illustratively, the bolus fluid reservoir 80 is in fluid communicationwith the pump chamber 54 associated with the second reservoir 14. Assuch, advancement of the toothed gear 66 of the bolus drive mechanism282 to advance the bolus drive piston 78 exerts a pressure on the drivenpiston 58 to advance the driven piston 58 and to deliver a bolus amountof the second medicament 22 through the needle 34.

Similar to the fluid delivery device 710, the fluid delivery device 810shown in FIG. 9 provides a basal delivery of the first and secondmedicaments 20, 22 while providing a bolus delivery of only the secondmedicament 22. The basal delivery of both of the first and secondmedicaments 20, 22 is provided through the use of a single basal drivemechanism 846. A first flow restrictor 856 fluidly connects the basalfluid reservoir 52 and the pump chamber 54 associated with first drugreservoir 12 while a second flow restrictor 858 fluidly connects thebasal fluid reservoir 52 and the pump chamber 54 associated with thesecond drug reservoir 14.

Further illustratively, the basal drive mechanism 846 is positionedbetween the pump chambers 54 and the first and second drug reservoirs12, 14 containing the first and second medicaments 20, 22. As such,neither flow restrictor 856, 858 is positioned upstream or downstreamfrom the other. While the single basal drive mechanism 846 is provided,it is also within the scope of this disclosure for the fluid deliverydevice 810 to include the single basal drive mechanism 346 shown inFIGS. 4 and 5, for example. The bolus drive mechanism 282 of the fluiddelivery device 810 provides a bolus delivery of only the secondmedicament 22. Of course, the dimension(s) of many of the components ofthe fluid delivery devices 710, 810 may be varied in order to provide adevice wherein the basal delivery of the first and second medicaments20, 22 are different from each other.

Looking now to FIGS. 10 and 11, fluid delivery devices 910, 1010 of thepresent disclosure are provided. Devices 910, 1010 are similar to thefluid delivery devices discussed above. As such, like reference numeralsare used to denote like components. Each of the fluid delivery devices910, 1010 provides only a basal delivery of both the first and secondmedicaments 20, 22. Therefore, looking first to FIG. 10, the fluiddelivery device 910 includes the first and second basal drive mechanisms46, 60 associated with the respective first and second drug reservoirs12, 14 to provide independent basal delivery of each of the first andsecond medicaments 20, 22. No bolus function is provided for either thefirst or second medicaments 20, 22. Illustratively, the fluid deliverydevice 910 shown in FIG. 10 provides the basal delivery of the first andsecond medicaments 20, 22 using two separate basal drive mechanisms 46,60. However, a single basal drive mechanism 846 may be used to providethe basal delivery of the first and second medicaments 20, 22, as shownby the fluid delivery device 1010 in FIG. 11, for example. Again, nobolus delivery function is provided for the device 1010 of FIG. 11. Ofcourse, the dimension(s) of many of the components of the fluid deliverydevices 910, 1010 may be varied in order to provide a device wherein thebasal delivery of the first medicament 20 is different from the basaldelivery of the second medicaments 22.

Looking now to FIGS. 12 and 13, fluid delivery devices 1110, 1210 of thepresent disclosure are provided. The devices 1110, 1210 are similar tothe fluid delivery devices discussed above. As such, like referencenumerals are used to denote like components. Each of the fluid deliverydevices 1110, 1210 provides only a bolus delivery of both the first andsecond medicaments 20, 22 and does not provide a basal delivery ofeither of the first and second medicaments 20, 22. Therefore, lookingfirst to FIG. 12, the fluid delivery device 1110 includes one bolusdrive mechanism 62 associated with each of the respective first andsecond drug reservoirs 12, 14 to provide bolus delivery of each of thefirst and second medicaments 20, 22. No basal delivery function isprovided for either of the first or second medicaments 20, 22. Lookingnow to FIG. 13, the fluid delivery device 1210 includes first and secondbolus drive mechanisms 280, 282 associated with the respective first andsecond drug reservoirs 12, 14 to provide separate bolus delivery of eachof the first and second medicaments 20, 22. Again, no basal deliveryfunction is provided for either the first or second medicaments 20, 22.Of course, the dimension(s) of many of the components of the fluiddelivery devices 1110, 1210 may be varied in order to provide a devicewherein the bolus delivery of the first medicament 20 is different fromthe bolus delivery of the second medicaments 22. For example, the sizeor diameter of one or both of the bolus pistons 78 may be varied such asthat shown in the fluid delivery device 450 of FIG. 5 b.

Looking now to FIG. 14, a fluid delivery device 1310 provides a basaldelivery of the second medicament 22 and a bolus delivery of the firstmedicament 20. Illustratively, no basal delivery is provided for thefirst medicament 20 while no bolus delivery is provided for the secondmedicament 22. Such an arrangement may be beneficial where only basaldelivery of a first medicament is desired while only supplemental bolusdelivery of the second medicament desired. It is within the scope ofthis disclosure to provide a fluid delivery device capable of providinga basal delivery of only the first medicament 20 while providing a bolusdelivery of only the second medicament 22, for example. Illustratively,the fluid delivery device 1310 shown in FIG. 14 includes the bolus drivemechanism 280 associated with the first fluid reservoir 12 and the basaldrive mechanism 60 associated with the second fluid reservoir 14.

The fluid delivery devices 10, 110, 210, 310, 410, 510, 550, 610, 710,810, 910, 1010, 1310, and 1410 described above each include one or moreof the basal fluid reservoirs 52, 352 fluidly coupled to one or morepump chambers 54 by a flow restrictor, such as flow restrictors 56, 356,357, 358, 856, 858. Illustratively, the fluid reservoirs 52, 352 eachdefine an inner chamber wherein the respective basal drive piston 50 ofthe particular basal drive mechanism is positioned within the innerchamber. However, other various basal fluid reservoirs which in fluidcommunication with one or more pump chambers may be provided as well.For example, looking to FIGS. 15 and 16, fluid delivery devices 1410 and1510 are provided which each include a flexible, balloon-type fluiddelivery reservoir 1452 containing hydraulic fluid, such as oil,therein.

Looking specifically to FIG. 15, two separate fluid delivery reservoirs1452 are provided which are each associated with one of the first andsecond fluid reservoirs 12, 14. Further an alternative basal drivemechanism 1446 is provided to force fluid from the respective basalfluid reservoir 1452 through the flow restrictor 56 and into the pumpchamber 54. Illustratively, each basal drive mechanism 1446 includes ahinged plate member 1450 coupled to the respective flexible basal fluidreservoir 1452. The hinged plate member 1450 may be compressed by aspring 1460 or other external force in order to force hydraulic fluidfrom within the reservoir 1452 through the flow restrictor and into thepump chamber 54 to advance the drive piston 58 and provide a basaldelivery of the first medicament 20, for example. While the hinged platemember 1450 and spring 1460 are disclosed, it is within the scope ofthis disclosure to provide other suitable drive mechanisms forcompressing the flexible basal fluid reservoir 1452.

As shown in FIG. 15, the first and second basal drive mechanisms 1446,1460 operate to compress the respective flexible basal fluid reservoir1452 in order to provide a basal delivery of each of the first andsecond medicaments 20, 22. Alternatively, a single basal drive mechanism1446 of the fluid delivery device 1510 shown in FIG. 16 operates toprovide a basal delivery of both the first and second medicaments 20,22.

Illustratively, any of the fluid delivery devices disclosed herein mayinclude basal and/or bolus drive mechanisms including a hinged platemember and a compressible fluid reservoir such as that shown in FIGS. 15and 16. It is also within the scope of this disclosure to include othersuitable drive mechanisms for advancing a fluid through a flowrestrictor. For example, a gas drive mechanism may generate gas, such asoxygen, for example, which exerts a force on either a piston, such asthe basal and bolus drive pistons described herein, or which exerts aforce on a flexible membrane to push a hydraulic liquid through a flowrestrictor to then advance the medicament to be delivered.Alternatively, such a flexible membrane may directly force themedicament through a needle or other such infusion device. Further, aspring compressed bellows crank, a paired roller set, or other mechanismto force hydraulic fluid (from a fluid reservoir, for example) through aflow restrictor and into a pump chamber to thereby exert a pressure on amovable barrier within a drug delivery chamber to expel at least somefluid from within the drug delivery chamber through an aperture of thedrug delivery chamber may be provided.

Looking now to FIG. 17, a fluid delivery device 1610 is provided. Thefluid delivery device 1610 is similar to the fluid delivery devicesdescribed above. As such, like reference numerals are used to denotelike components. A flexible member 1658 of the fluid delivery device1610 has replaced the driven piston 58 of previous embodiments. Theflexible member 1658 is able to deform in response to the pressureexerted upon it from hydraulic fluid forced into the pump chamber 54from either the basal fluid reservoir 52 through the flow restrictor 56or from the bolus fluid reservoir 80. The deformation of the flexiblemember 1658 into the drug reservoir 12 forces the first medicament 20within the reservoir 12 through the needle 32.

Illustratively, the flexible member 1658 as well as the piston 58described in previous embodiments operate as barrier mechanisms betweenthe one of the medicaments 20, 22 and the hydraulic fluid exertingpressure onto the barrier mechanism. Although the piston 58 and theflexible member 1658 have been specifically disclosed herein, it iswithin the scope of this disclosure to include other such suitablebarrier mechanisms separating the medicament 20, 22 from the hydraulicfluid. At least a portion of such barrier mechanisms are capable ofmoving within the inner chamber of the fluid reservoir relative to theouter walls of the fluid reservoir in order to force medicament out ofthe fluid reservoir. Various other barrier mechanisms are described ingreater detail in U.S. Pat. No. 6,969,324 and U.S. Patent ApplicationPublication No. US 2005/0119618, the disclosures of which are herebyincorporated by reference herein.

Each of the fluid delivery devices described above includes a firstneedle 32 in fluid communication with the reservoir 12 containing thefirst medicament 20 and a second needle 34 in fluid communication thereservoir 14 containing with the second medicament 22. These separateneedles 32, 34 may be spaced-apart from each other a desired distance inorder to prevent any mixing or commingling of the first and secondmedicaments 20, 22 once the medicaments are introduced subcutaneouslyinto the patient. It is often desirable, for example, to prevent anymixing of two different medicaments before delivery, during delivery,and after delivery of the medicaments into the patient if and when theremay be compatibility issues between the two medicaments, for example. Assuch, the needles 32, 34 may be positioned at opposite ends of therespective fluid delivery device in order to maximize the distancebetween the two medicaments when each is delivered into the patient.

Additionally, or as an alternative, the first needle 32 may be providedwith a delivery arm 142 which is significantly longer than the deliveryarm 42 of the second needle 34, as shown in FIG. 18, for example. Assuch, the delivery arm 142 of the first needle 32 will be inserted to agreater subcutaneous depth within the patient than the delivery arm 42of the second needle 34. In such an instance, the first medicament 20 isdelivered to the patient at a different subcutaneous depth than thesubcutaneous depth to which the second medicament 22 is delivered. Byvarying the depth to which the delivery end of the needles 32, 34 areinserted within a patient, the first and second medicaments 20, 22 maybe substantially prevented from mixing once injected into the patient.

Illustratively, therefore, separate needles 32, 34 may be used toseparately deliver the first and second medicaments 20, 22. In instanceswhere there may be compatibility issues between the two medicaments 20,22, the needles 32, 34 may be spaced-apart from each other a suitabledistance to substantially prevent any mixing of the medicaments 20, 22during and after delivery of the medicaments 20, 22 to the patient.Additionally, or as an alternative, the needles 32, 34 may be insertedinto the patient at different depths to further prevent any mixing ofthe medicaments 20, 22 during or after delivery of the medicaments 20,22.

Looking again to FIG. 18, a needle cover button 200 is provided whichillustratively houses both needles 32, 34 therein. As such, actuation ofthe needle cover button 200 by a user or patient actuates both needles32, 34 at the same time. Illustratively, in operation, the needles 32,34 are positioned in a first, un-activated position (not shown) wherebythe uptake arm 40 of each needle 32, 34 is spaced apart from therespective stoppers 24, 28. Further, the delivery arm 142, 42 of eachneedle 32, 34 is contained within an external housing (not shown) of thefluid delivery device. In order to move the needles to an activatedposition, a user depresses the button 200 to lower each needle 32, 34such that the uptake arm 40 of each needle 32, 34 pierces the respectivestopper 24, 28 and is in fluid communication with the hollow chamber 26containing the respective first and second medicaments 20, 22, as shownin FIGS. 1-17, for example. Further, in the activated position thedistal end 38 of the delivery arm 142, 42 of each needle 32, 34 extendsbeyond the external housing of the delivery device for subcutaneousplacement within the patient. Although the single needle cover button200 is shown in FIG. 18, it is within the scope of this disclosure toinclude a separate needle cover button associated with each needle 32,34 such that the needles 32, 34 may be activated separately.

Looking now to FIG. 19, a generally “Y-shaped” needle 232 is providedand may be used with one or more of the delivery devices disclosedherein. Illustratively, the needle 232 includes a single delivery arm242, a first uptake arm 244 spaced-apart from and illustrativelyparallel to the delivery arm 242, and a second uptake arm 246spaced-apart from and illustratively parallel to the delivery arm 242 aswell. A respective first and second transverse or connector arm 248, 250couples each of the uptake arms 244, 246 to the delivery arm 242. Theneedle 232 is cannulated to define a continuous passageway extendingthrough each of the arms 242, 244, 246, 248, 250. In an activatedposition, the first end 36 of each uptake arm 244, 246 is receivedthrough an outer wall of the respective first and second stoppers 24, 28of the various fluid delivery devices disclosed herein. As such, thefirst end 36 of each uptake arm 244, 246 is positioned within the hollowchamber 26 of each stopper 24, 28 when the needle 232 is in theactivated position. The second end 38 of the delivery arm 242 of theneedle 232 is provided for subcutaneous insertion into a patient inorder to deliver the first and second medicaments 20, 22 to the patient.

Illustratively, the needle 232 permits the first and second medicaments20, 22 to mix with each other prior to being delivered into the patient.For example, the first medicament 20 may enter the uptake arm 244 of theneedle 232 and travel along the transverse arm 248 to the delivery arm242. The second medicament 22 may similarly enter the uptake arm 246 ofthe needle 232 and travel along the transverse arm 250 to mix with thefirst medicament 20 in the delivery arm 242. The needle 232 may be usedwith delivery devices where the first and second medicaments 20, 22contained within such delivery devices are compatible with each otherand may be mixed prior to delivery into the patient. Of course, withseparate basal and bolus delivery mechanisms, there may be instanceswhere only the first medicament 20 or only the second medicament 22 isbeing delivered through the needle 232.

While the “Y-shaped” needle 232 is disclosed herein for use withcompatible medicaments able to be mixed together, it should beunderstood that other suitable needles may be used which permit themedicaments to mix with each other after leaving the fluid reservoirswithin which each is stored. For example, it is to be understood thatY-shapes are intended to encompass T-shapes. Further illustratively, acover button 252 is shown in FIG. 19 to cover and maintain the needle232 in the un-activated position until the button 252 is depressed oractivated by a user or patient. Further, upon depressing the coverbutton 252, the needle 232 may be moved to the activated position toallow fluids from the first and second reservoirs 12, 14 to enter therespective uptake arms 244, 246.

According to one aspect of the present disclosure, a fluid deliverydevice may include a plurality of drug reservoirs for containing anddelivering a plurality of different medicaments. For example, while thefluid delivery devices described above and shown in FIGS. 1-17, includefirst and second medicaments 20, 22 contained within first and secondreservoirs 12, 14, it is within the scope of this disclosure to includea fluid delivery device having a third medicament contained within athird reservoir. A separate or shared basal drive mechanism may beassociated with the third reservoir containing the third medicamentwhile a separate or shared bolus drive mechanism may also be associatedwith the third reservoir containing the third medicament. Further, ashared or separate needle may also be associated with each of the first,second, and third medicaments to deliver each medicament separately orcombined. Similarly, it is within the scope of this disclosure toinclude a fluid delivery device having more than three medicaments eachcontained within separate fluid reservoirs.

According to another aspect of the present disclosure, the deliverydevices disclosed herein are relatively compact, portable, and able tobe fixed to the user or patient during use and subsequently disposed ofwhen the treatment is finished. Of course, other such non-portable andnon-disposable delivery devices are included within the scope of thisdisclosure as well.

According to still another aspect of the present disclosure, the fluiddelivery devices described herein are adapted to deliver two differentmedicaments 20 and 22. In one embodiment, the first and secondmedicaments 20, 22 are selected as being adapted for treating twodifferent diseases that may occur in a co-morbid disease state. Inanother embodiment, the first and second medicaments 20, 22 are selectedas being adapted for treating two different symptoms that may be presentin a single disease. In another embodiment, the first and secondmedicaments 20, 22 are selected as being adapted for treating the samedisease and/or symptom where such a combination of such two or moremedicaments may be contemplated or desirable.

In another embodiment, the first and second medicaments 20, 22 areselected as being adapted for treating a disease state where forexample, one of the first or second medicaments 20, 22 causesundesirable or unwanted side effects or other adverse events, and theother of the first and second medicaments 20, 22 mediates, ameliorates,or alleviates those side effects or adverse events.

In another embodiment, the first and second medicaments 20, 22 areselected as being adapted for treating a disease state where theefficacy or performance of one of the first or second medicaments 20, 22is enhanced or improved by the co-administration of the other of thefirst or second medicaments 20, 22. Efficacy enhancement may be additiveor synergistic, or may correct for or mediate sensitization,desensitization or tolerance that may accompany the use of one of thefirst or second medicaments 20, 22. It is appreciated that suchenhancement or improvement may lead to the lowering of the overallamount of the medicament whose efficacy or performance is enhanced.

It is understood that the devices described herein may allow for thepairing of two medicaments that otherwise could not be delivered in aunitary dosage form by conventional means. For example, certain pairingsof medicaments may not be possible in conventional unitary dosage formsdue to chemical incompatibility, differential stability requirements,different formulation requirements, and other optimization parametersneeded for efficacy. Further, certain pairings of medicaments may not bepossible in conventional unitary dosage forms due to the need forflexibility in altering the ratio of the first and second medicaments.It is suggested that conventional dosage forms would require a fixedratio. Further, certain pairings of medicaments may not be possible inconventional unitary dosage forms due to complicated dosing regimensrequiring alternate administration over predetermined time periods. Itis to be further understood that though the foregoing describes drugpairings, those aspects apply equally to embodiments of the deliverydevices described herein that are configured to deliver three or moremedicaments.

In one embodiment, the devices described herein are adapted fordelivering medicaments to treat diabetes, including Type I and Type IIdiabetes, diabetic symptoms, and diabetic conditions.

In one embodiment, the first or second medicament 20, 22 is insulin oran insulin analog, and the other medicament 20, 22 is drug selected toimprove the performance, or decrease the side effect profile of theinsulin or insulin analog. It is to be understood that the first andsecond medicaments 20, 22 may each refer to the insulin or analogthereof. For example, as used herein, insulin analogs includepro-insulin, pre-insulin, and insulins that have been modified withvarious amino acids, such as with insertions, deletions, andsubstitutions. The devices described herein include various options asto the presence or absence of bolus and/or basal delivery, the relativesize of the bolus delivery, the relative rate of the basal delivery, andother features. Accordingly, in some embodiments of the devices, theinsulin or insulin analog is the first medicament 20, while in otherembodiments, the insulin or insulin analog is the second medicament 22.Accordingly, as used throughout the terms first medicament 20 and secondmedicament 22 may be interchanged with the identification of themedicament for different configurations and embodiments of the devicesdescribed herein.

In another embodiment, both natural and synthetic insulins and insulinanalogs may be used as the first or second medicament 20, 22. In oneaspect, insulins used are naturally occurring, such as naturallyoccurring human insulins and analogs thereof, including but not limitedto those produced using recombinant methods from other organisms such asbacteria. In another aspect, insulins used are synthetic insulins, ormodified insulins including amino acid chain modifications such asinsertions, deletions, and exchanges in the insulin sequence.Illustratively, the insulins are Lispro insulin, Aspart insulin,Glargine insulin, Detemir insulin, and the like. Further, insulinsinclude but are not limited to the amino acid insertions, amino aciddeletions, and amino acid substitutions of various insulins from humanand other sources. It is understood that such modifications may be madeon the A or B chains. Illustratively, insulins may be included asmedicaments 20, 22 herein, where Asp28 on the B-chain is substituted,such as with Pro28 or Lys28; where Lys29 in the B-chain is substitutedwith Pro29 or Glu29; where the B-chain is extended, such as with Arg31or Arg31-Arg32; where Asn 21 on the A-chain is substituted, such as withGly21; where Asn3 on the B-chain is substituted, such as with Lys3; andsimilar modifications.

In another aspect, insulins used as medicaments herein are intermediateacting insulins, including but not limited to HUMULIN L, HUMULIN N,NOVOLIN N, NOVOLIN R, and the like. In another aspect, insulins used asmedicaments herein are rapid acting insulins, including but not limitedto APIDRA, HUMALOG HUMULIN R, NOVOLIN R, NOVOLOG, and the like. Inanother aspect, insulins used as medicaments herein are long actinginsulins, including but not limited to HUMULIN U, LANTUS, and the like.In another aspect, insulins used as medicaments herein are mixtures ofvarious insulins, including but not limited to HUMALOG MIX 75/25,HUMULIN 50/50, HUMULIN 70/30, NOVOLIN 70/30, NOVOLOG MIX 70/30, and thelike.

In one variation, both medicaments 20, 22 are insulins. It isappreciated that more varied mixtures of insulins may be delivered tocertain patients using configurations where the first medicament 20 isone insulin, and the second medicament 22 is another insulin. It isunderstood that insulins may be selected to suit the needs of varioussubpopulations of patients for which readily available premixed insulinsare less desirable, or where mixing insulins is not desirable. Inanother aspect the first insulin is long acting insulins such as HUMULINU, LANTUS, and the like, and the second insulin is an intermediate orshort acting insulin, as described herein. In one configuration, thedevice is selected such that both the first and second medicaments 20,22 are primarily or exclusively adminstered to the patient in a bolusmanner rather than a basal manner. In those configuration, it isunderstood that for example, the long acting insulin may be administeredas a once-per-day bolus amount, and the short or intermediate actinginsulin is administered in a meal-time ready bolus amount. In onevariation it is contemplated that the short or intermediate actinginsulin may be administered in a basal manner as well, or in anothervariation the short or intermediate acting insulin may be administeredin a basal manner over a shortened period of time to correspond withmeal time.

In an alternate embodiment, the other medicament 20, 22 may be includedto increase the efficacy of, improve the performance of, or decrease theside effect profile of the insulin or insulin analog used as amedicament. The mechanisms for this increased insulin efficacy orimproved performance may be any, including improving endogenous insulinproduction, decreasing insulin resistance or insulin insensitivity,improving the utilization of insulin and glucose by peripheral tissues,increasing the uptake of glucose by peripheral tissues, decreasing theamount or slowing the rate of endogenous sugar production from certainorgans, including but not limited to the liver, decreasing the amount orslowing the rate of gastrointestinal sugar absorption, and the like.

In one configuration, the other medicament is an incretin, incretinmimetic or incretin analog, such as glucagon-like-peptide (GLP), a GLP-1analog, exenatide (BYETTA, Amylin, Lilly), Extendin-4, and the like.Incretin mimetics and/or incretin analogs may act analogous toGlucagon-Like Peptide-1 (GLP-1), a naturally occurring peptide whichenhances insulin secretion in response to elevated plasma glucoselevels, may be included as helper drugs. It is understood that the GLP-1system increases insulin secretion only in the presence of elevatedplasma glucose levels, avoiding inappropriately high insulin levelsduring fasting. It is appreciated that incretins may enhanceglucose-dependent insulin secretion and exhibit other antihyperglycemicactions following their release into the circulation. Incretins may alsomoderate peak serum glucagon levels during hyperglycemic periodsfollowing meals, without interfering with glucagon release in responseto hypoglycemia. Incretins may also have beneficial secondary effects ofreducing the rate of gastric emptying and decrease food intake,mitigating the potential severity of hyperglycemic events after meals.In one embodiment, the devices described herein include a daily dose ofBYETTA in the range from about 5 to about 10 micrograms. In theforegoing configuration, it is appreciated that devices may be selectedthat include a separate needle for each of the reservoirs containingmedicaments 20, 22, such that substantial mixing of the two medicamentsdoes not occur at, or optionally near, the sites of injection.

In another configuration, the other medicament is an amylin peptide,such as pramlintide (SIMLYN, Amylin). It is appreciated thatdeficiencies in insulin may parallel deficiencies in amylin. Amylin mayhave a moderating effect on blood glucose absorption from the gut intothe blood, slowing and managing meal-derived glucose inflow, controllingpancreatic glucagon secretion, and consequently regulating hepaticglucose production. In the foregoing configuration, it is appreciatedthat devices may be selected that include a separate needle for each ofthe reservoirs containing medicaments 20, 22, such that substantialmixing of the two medicaments does not occur at, or optionally near, thesites of injection.

In another configuration, the other medicament is a biguanide orbiguanide combination In one illustrative aspect, the biguanide ismetformin (GLUCOPHAGE, FORTAMET, RIOMET). In another illustrativeaspect, the biguanide is an inhibitor of hepatic glucose production. Inanother aspect, the biguanide is an inhibitor of gastrointestinalglucose absorption. It is appreciated that biguanides may increase theefficacy of insulin therapy by decreasing hepatic glucose production,decreasing intestinal absorption of glucose, and/or increasingperipheral glucose uptake and utilization. In one variation,pharmaceutically acceptable salts of such medicaments are included inthe devices described herein.

In another configuration, the other medicament is a glucosidaseinhibitor, such as acarbose (PRECOSE, Bayer), and the like. It isappreciated that glucosidase inhibitors may increase the efficacy ofinsulin therapy by slowing either the pancreatic and/or intestinalhydrolysis of complex carbohydrates to glucose.

In another configuration, the other medicament is a sulfonylurea, suchas Amaryl glimepiride (AMARYL, Aventis), glyburide (DIABETA, Aventis),glipizide (GLUCOTROL, Pfizer), and like insulin secretagogues. It isappreciated that sulfonylureas may increase the efficacy of insulintherapy by increasing the amount of endogenous insulin secretion, suchas from pancreatic beta cells. In addition, sulfonylureas may increasethe efficacy of insulin therapy by increasing the sensitivity ofperipheral tissues to insulin.

In another configuration, the other medicament is a meglitinide, such asrepaglinide (PRANDIN, Novo Nordisk), nateglidine (STARLIX, Novatis), andlike insulin secretagogues. It is appreciated that meglitinides mayincrease the efficacy of insulin therapy by increasing the amount ofendogenous insulin secretion, such as from pancreatic beta cells, byblocking ATP-dependent potassium channels.

In another configuration, the other medicament is an agonist of aperoxisome proliferator activated receptor (PPAR) such as PPARγ. In oneembodiment, the PPARγ agonist is a thiazolidinedione (TZD) insulinsensitizer, including but not limited to pioglitazone (ACTOS, Takeda),AVANDAMET (GlaxoSmithKline), rosiglitazone maleate (AVANDIA,GlaxoSmithKline), phenformin, buformin, and the like. It is appreciatedthat TZD insulin sensitizers and other PPARγ agonists may increase theefficacy of insulin therapy by decreasing insulin resistance orinsensitivity in peripheral tissues and in the liver, resulting inincreased insulin dependent glucose disposal and decreased hepaticglucose output. It is appreciated that compounds that also lack PPARαbinding action may be advantageously included in the devices describedherein.

In another configuration, mixtures of such other medicaments arecontemplated. Illustratively, the mixture may be of a TZD insulinsensitizer or PPARγ agonist and a biguanide, such as metformin mixedwith rosiglitazone maleate (AVANDAMET, GlaxoSmithKline), and likemixtures. It is appreciated that other drugs that reduce hepaticgluconeogenesis may be included alone or in combination with TZDs. It isalso appreciated that other drugs that decrease intestinal absorption ofglucose may be included alone or in combination with TZDs. It is alsoappreciated that other drugs that improves insulin sensitivity byincreasing peripheral glucose uptake and utilization may be includedalone or in combination with TZDs. In addition, the mixture may be of anincretin mimetic or incretin analog and a biguanide or sulfonyl urea,such as exenatide mixed with metformin or glimepiride, and likemixtures. In addition, the mixture may be of a biguanide and asulfonylurea, such as metformin mixed with glipizide (METAGLIP, BristolMeyers Squibb), and like mixtures.

In another configuration, the other medicament is a saccharide, such asa glucagon or an analog thereof. It is appreciated that during insulinadministration with the devices described herein, it may be desirable ornecessary to moderate and/or lessen the impact of insulin administrationthat may result in hypoglycemia or a hypoglycemic condition. It isfurther appreciated that the administration of such a saccharide may becontrolled by the basal functions of the devices described herein, oralternatively by the bolus functions of the devices described herein.For example, in one illustrative embodiment, upon the onset ofhypoglycemia or a hypoglycemic condition, the patient being treated mayinitiate a bolus administration of the saccharide. It is understood thatthe onset of hypoglycemia or a hypoglycemic condition may be determinedusing any conventional method of monitoring blood-glucose levels,including but not limited to blood-glucose strips, and the like. In onevariation, the onset of hypoglycemia or a hypoglycemic condition may bedetermined by the patient through training, and/or experience inrecognizing certain symptoms indicating such hypoglycemia or ahypoglycemic condition. It is further understood that in otherconfigurations, it is less desirable to have any sustained levels ofglucagon administration, and therefore one variation of this embodimentwould include bolus delivery of the saccharide as the primary orexclusive route of administration.

In another configuration, the other medicament is insulin-like growthfactor (IGF) 1 or 2, or an analog or derivative thereof. It isappreciated that IGF-1 and/or IGF-2 may be administered with insulin, oranalogs thereof, to decrease hypoglycemia and/or hypoglycemic conditionsthat may be caused by insulin administration alone. IGF-1 and IGF-2 bindto insulin receptors, but with much lower affinity than does insulin,such as at about 10-fold or even 100-fold less affinity than insulin.Without being bound by theory, it is suggested co-administration ofIGF-1 or IGF-2, or an analog or derivative thereof, may decrease insulinsensitivity and therefore may decrease the potential for the onset ofhypoglycemia and/or hypoglycemic conditions caused by insulinadministration. It is understood that IGF-1 and IGF-2 may be rapidlybound to binding proteins upon administration. Accordingly, ligandconjugates of IGF-1 and IGF-2, and their analogs, are also contemplatedherein. Such ligand conjugates may increase the overall bioavailabilityof the IGF-1 and IGF-2, or analog thereof that is administered asdescribed herein.

In another configuration, the other medicament is C-peptide, or ananalog thereof. It is understood that in endogenous insulin productionand metabolism, pro-insulin is made in the β-cells and once release itis cleaved by peptidases to release the C-peptide fragment. Finally,carboxypeptidase E produces the mature insulin by truncating theterminus of the B-chain. It is appreciated that C-peptide may beco-administered with the insulin, or any analog or derivative thereof,as the second medicament. Without being bound be theory, it is suggestedthat C-peptide is useful in regulation of glucose metabolism and also inother biologically important processes, and therefore, the complete ornear complete replacement of endogenous insulin with exogenous sourcesmay lead to an undesirable level of C-peptide. For example, neuropathyis a co-morbid pathology that may accompany diabetes or other diabeticconditions or condition of glucose dysregulation. Thus, it is suggestedthat C-peptide administration may treat neuropathy, decrease theprogression of neuropathy, or delay or halt the onset of neuropathy. Itis appreciated that the devices described herein may lead to betterpatient compliance than conventional methods, including conventionalmethods that include administering C-peptide by injection.

In one aspect, the C-peptide, or analog or derivative thereof, isadministered to the patient at a ratio of about 1:1 on a molar basiscompared to the insulin, thus mirroring the endogenous condition inhealthy patients. In another aspect, the C-peptide, or analog orderivative thereof, is administered to the patient at a ratio of lessthan 1:1 on a molar basis compared to the insulin. In this latterembodiment, it is understood that levels of C-peptide may not need to bemaintained as high as those of insulin to treat diabetes and associatedconditions. In addition, it is understood that C-peptide administrationmay lead to a plateau effect, and accordingly, patient needs forC-peptide may decrease over time. Thus, in this alternate aspect, theC-peptide, or analog or derivative thereof, is administered to thepatient at a ratio of about 4:5, about 3:4, about 2:3, or about 1:2 on amolar basis compared to the insulin.

In addition, it is appreciated that though the foregoing embodimentwhere the second medicament is C-peptide, or an analog or derivativethereof, may be administered using any of the devices described herein,in one variation, devices are selected that include a single needle,whereby both medicaments 20, 22 mix prior to administration. In anothervariation, devices are selected that include two or more needles, whereat least two of such needles are located proximally to the other, thusallowing both medicaments 20, 22 to mix immediately or soon afteradministration at the site of entry into the patient.

In another configuration, the first and second medicaments 20, 22 areboth anti-infective compounds. In one aspect, the anti-infectivecompounds are antibacterial agents, such as penicillins and relatedcompounds, including carbacephems, carbapenems, cephalosporins, and thelike, monobactams, polypeptides, aminoglycosides, glycopeptides,vancomycins, macrolide antibiotics including erythromycins, quinolones,sulfonamides, tetracyclines, and the like.

Illustrative aminoglycosides that may be included in the devicesdescribed herein include, but at not limited to, amikacin, gentamicin,kanamycin, neomycin, netilmicin, streptomycin, tobramycin, and the like.Illustrative carbacephems include loracarbef and the like. Illustrativecarbapenems include ertapenem, imipenem, cilastatin, meropenem, and thelike. Illustrative cephalosporins include first, second, third, andfourth generation cephalosporins, such as cefadroxil, cefazolin,cephalexin, cefaclor, cefamandole, cefoxitin, cefprozil, cefuroxime,cefixime, cefdinir, cefditoren, cefoperazone, cefotaxime, cefpodoxime,ceftazidime, ceftibuten, ceftizoxime, ceftriaxone, cefepime, and thelike.

Illustrative macrolides that may be included in the devices describedherein include, but at not limited to, azithromycin, clarithromycin,dirithromycin, erythromycin, roxithromyucin, troleandomycin, and thelike. Illustrative glycopeptides that may be included in the devicesdescribed herein include teicoplanin, vancomycin, and the like.Illustrative penicillins include amoxicillin, ampicillin, azlocillin,cabenicillin, cloxacillin, and the like, and monobactams includeaztreonam, and the like. Illustrative polypeptides include bacitracin,colistin, polymyxin B, and the like.

Illustrative quinolones includes ciprofloxacin, enoxacin, gatifloxacin,levofloxacin moxifloxacin, and the like. Illustrative sulfonamidesinclude mafenide, sulfacetamide, sulfamethizole, sulfasalazine,sulfisoxazole, trimethoprim, BACTRIM, and the like. Illustrativetetracyclines include demeclocycline, doxycycline, minocycline,oxytetracycline, tetracycline, and the like. Still other illustrativeantibiotics that may be included in the devices described hereininclude, but at not limited to, arsphenamine, chloramphenicol,floramphenicol, clindamycin, ethambutol, fosfomycin, furzolidone,isoniazid, linezolid, metronidazole, nitrofurantoin, rifampin,spectinomycin, telithromycin, and the like.

In another embodiment, the first and second medicaments 20, 22 areagonists or antagonists of neurotransmitter receptors. In oneillustrative aspect, the first medicament is dopamine or a dopaminereceptor agonist, and the second medicament is a dopamine receptorantagonist. Illustrative dopamine receptor agonists and antagonists aredescribed in PCT international application serial No. PCT/US2004/043145,the disclosure of which is incorporated herein in its entirety byreference. In one aspect, the dopamine agonist is selective for thedopamine D₁ receptor. In another aspect, the dopamine antagonist isselective for the dopamine D₂ receptor. It is appreciated that theco-administration of a dopamine D₂ receptor antagonist may enhance orimprove the efficacy or overall benefit of the dopamine receptoragonist, including dopamine D₁ receptor agonists. It is also appreciatedthat the co-administration of a dopamine D₂ receptor antagonist maydecrease, ameliorate, or alleviate side effects associated with thedopamine receptor agonist, including dopamine D₁ receptor agonists.

Illustrative dopamine D₂ receptor antagonists that may be included inthe devices described herein include, but at not limited to, compoundsof the formulae:

and pharmaceutically acceptable salts thereof, wherein R is hydrogen orC₁-C₄ alkyl; R¹ is hydrogen, acyl, such as C₁-C₄ alkanoyl, benzoyl,pivaloyl, and the like, or an optionally substituted phenyl or phenoxyprotecting group, such as a prodrug and the like; X is hydrogen, fluoro,chloro, bromo, iodo or a group of the formula —OR⁸ wherein R⁸ ishydrogen, C₁-C₄ alkyl, acyl, such as C₁-C₄ alkanoyl, benzoyl, pivaloyl,and the like, or an optionally substituted phenyl or phenoxy protectinggroup, provided that when X is a group of the formula —OR⁸, the groupsR¹ and R⁸ can optionally be taken together to form a —CH₂— or —(CH₂)₂—group, thus representing a methylenedioxy or ethylenedioxy functionalgroup; R^(A), R², R³, R⁴, R⁵, R⁶, and R⁷ are each independently selectedfrom hydrogen, C₁-C₄ alkyl, phenyl, fluoro, chloro, bromo, iodo, and agroup —OR⁹ wherein R⁹ is hydrogen, acyl, such as C₁-C₄ alkanoyl,benzoyl, pivaloyl, and the like, or an optionally substituted phenyl orphenoxy protecting group; and R^(B) is selected from hydrogen, C₁-C₄alkyl, phenyl, fluoro, chloro, bromo, iodo, a group —OR⁹ wherein R⁹ ishydrogen, acyl, such as C₁-C₄ alkanoyl, benzoyl, pivaloyl, and the like,—OR¹ and X, as defined above, and optionally substituted phenyl orphenoxy protecting groups, providing that at least one of R^(B) is —OR¹.

Illustrative dopamine D₂ receptor antagonists that may be included inthe devices described herein include, but at not limited to,antipsychotic agents, illustratively selected from the typical andatypical families of antipsychotic agents. It is appreciated thatatypical antipsychotics may generally be associated with less acuteextrapyramidal symptoms, especially dystonias, and less frequent andsmaller increases in serum prolactin concentrations associated withtherapy. In one aspect, the typical antipsychotic agents includephenothiazines and non-phenothiazines such as loxapine, molindone, andthe like. In another aspect, the atypical antipsychotic agents includethe clozapine-like agents, and others, including aripiprazole,risperidone(3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidino]ethyl]-2-methyl-6,7,8,9-tetrahydro-4H-pyrido-[1,2-a]pyrimidin-4-one),amisulpiride, sertindole(1-[2-[4-[5-chloro-1-(4-fluorophenyl)-1H-indol-3-yl]-1-piperidinyl]ethyl]imidazolidin-2-one),and the like. Phenothiazines include, but are not limited tochlorpromazine, fluphenazine, mesoridazine, perphenazine,prochlorperazine, thioridazine, and trifluoperazine. Non-phenothiazinesinclude, but are not limited to haloperidol, pimozide, and thiothixene.Other clozapine-like agents include, but are not limited to olanzapine(2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benzodiazepine),clozapine(8-chloro-11-(4-methyl-1-piperazinyl)-5H-dibenzo[b,e][1,4]diazepine),quetiapine(5-[2-(4-dibenzo[b,f][1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]ethanol),ziprasidone(5-[2-[4-(1,2-benzoisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one),and the like. It is appreciated that other typical and atypicalantipsychotic agents may be used as the dopamine receptor antagonistdescribed herein. It is also appreciated that various combinations oftypical and atypical antipsychotic agents may be used.

The devices described herein may be configured to deliver daily dosageamounts of the various first and second medicaments 20, 22 atbioequivalency levels comparable to conventional drug formulations.Illustratively, metformin may be delivered at rates that correlate tothe conventional oral dosage of 500, 850, 1,000, or 2,000 mg/day. It isto be understood that the amount delivered by the parenteral routesdescribed herein for the various devices will often be substantiallylower than the equivalent oral dosage form. For example, metformin maybe delivered in a pulsatile or bolus delivery profile at a rate thatcorresponds to values that do not exceed the peak plasma concentration(C_(max)) observed for the oral dosage form, such in the range fromabout 0.5 to about 4 μg/mL. Alternatively, metformin may be delivered ina sustained or basal delivery profile at a rates lower than the C_(max),and corresponding to the average value under the area under curve (AUC),such as in the range from about 4 to about 10 μg·h/mL. These and othervalues for metformin, as well as for other first and second medicaments20, 22 described herein are found in and/or routinely derived fromvalues presented for the conventional dosage forms of such medicamentsin Physicians' Desk Reference, Thompson P D R, Montvale N.J. (59^(th)edition, 2005), the disclosure of which is incorporated herein byreference.

It is suggested that the devices described herein may be particularlyappropriate for basal delivery, or alternatively bolus delivery at morefrequent and lower doses, of medicaments that are deliveredconventionally once or twice per day due to formulation issues,convenience, or poor expected patient compliance. Accordingly, thedevices described herein may be configured to deliver pharmacokinetic(PK) profiles of medicaments that are not possible with conventionalformulations. For example, the peak-valley PK profile generallyaccompanying once a day dosing may be converted to a lower levelsustained release PK profile, or a lower peak-higher valley morefrequent pulsatile PK profile.

There are a plurality of advantages of the present disclosure arisingfrom the various features of the apparatus and methods described herein.It will be noted that alternative embodiments of the apparatus andmethods of the present disclosure may not include all of the featuresdescribed yet still benefit from at least some of the advantages of suchfeatures. Those of ordinary skill in the art may readily devise theirown implementations of an apparatus and method that incorporate one ormore of the features of the present disclosure and fall within thespirit and scope of the present disclosure.

1. A fluid delivery device for administering a first medicament and asecond medicament comprising: a housing; a first reservoir within thehousing and configured to contain the first medicament; a secondreservoir within the housing and configured to contain the secondmedicament; a first basal drive mechanism within the housing and havinga first hydraulic fluid reservoir; a first pump chamber in fluidcommunication with the first hydraulic fluid reservoir of the firstbasal drive mechanism via a first flow restrictor, the first pumpchamber configured to engage the first reservoir to provide a basaldelivery of the first medicament during use; a second basal drivemechanism within the housing and having a second hydraulic fluidreservoir; a second pump chamber in fluid communication with the secondhydraulic fluid reservoir of the second basal drive mechanism via asecond flow restrictor, the second pump chamber configured to engage thesecond reservoir to provide a basal delivery of the second medicamentduring use; and a needle having a first end configured for fluidcommunication with the first reservoir and a second end configured toextend exteriorly from the housing.
 2. The fluid delivery device ofclaim 1, wherein the first and second basal drive mechanisms eachinclude a coil spring coupled to a drive piston.
 3. The fluid deliverydevice of claim 1, further comprising a first delivery piston coupled tothe first pump chamber and positioned within the first fluid reservoirto exert a force on the first medicament within the first fluidreservoir and a second delivery piston coupled to the second pumpchamber and positioned within the second fluid reservoir to exert aforce on the second medicament within the second fluid reservoir.
 4. Thefluid delivery device of claim 1, further comprising a bolus drivemechanism coupled to the first pump chamber and configured to provide abolus delivery of the first medicament.
 5. The fluid delivery device ofclaim 1, wherein the needle includes a third end configured for fluidcommunication with the second reservoir.
 6. The fluid delivery device ofclaim 1, wherein the needle configured for fluid communication with thefirst reservoir is a first needle, the fluid delivery device furthercomprising a second needle configured for fluid communication with thesecond reservoir.
 7. The fluid delivery device of claim 1, wherein thedevice is an ambulatory infusion pump.
 8. The fluid delivery device ofclaim 4, wherein the bolus drive mechanism is coupled to the second pumpchamber and is configured to provide a bolus delivery of the secondmedicament.
 9. The fluid delivery device of claim 4, wherein the bolusdrive mechanism is a first bolus drive mechanism and wherein the fluiddelivery device further comprises a second bolus drive mechanism coupledto the second pump chamber and configured to provide a bolus delivery ofthe second medicament.
 10. The fluid delivery device of claim 4, whereinthe bolus drive mechanism includes a ratchet and a bolus piston coupledto the ratchet.
 11. The fluid delivery device of claim 8, wherein thebolus of the first medicament is larger than the bolus of the secondmedicament.
 12. A fluid delivery device for administering a firstmedicament and a second medicament comprising: a housing; a firstreservoir within the housing and configured to contain the firstmedicament; a second reservoir within the housing and configured tocontain the second medicament; a basal drive mechanism within thehousing and having a hydraulic fluid reservoir; a first pump chamber influid communication with the hydraulic fluid reservoir of the basaldrive mechanism via a first flow restrictor, the first pump chamberconfigured to engage the first reservoir to provide basal delivery ofthe first medicament during use; and a second pump chamber in fluidcommunication with the hydraulic fluid reservoir of the basal drivemechanism via a second flow restrictor, the second pump chamberconfigured to engage the second reservoir to provide basal delivery ofthe second medicaments during use.
 13. The fluid delivery device ofclaim 12, further comprising a bolus drive mechanism coupled to thefirst and second pump chambers to provide bolus deliveries of the firstand second medicaments.
 14. The fluid delivery device of claim 12,further comprising a first bolus drive mechanism coupled to the firstpump chamber to provide a bolus delivery of the first medicament and asecond bolus drive mechanism coupled to the second pump chamber toprovide a bolus delivery of the second medicament.
 15. The fluiddelivery device of claim 12, further comprising a needle having a firstend configured for fluid communication with the first reservoir, asecond end configured for fluid communication with the second reservoirand a third end configured to engage a user.
 16. The fluid deliverydevice of claim 12, further comprising a first needle configured forfluid communication with the first reservoir and a user and a secondneedle configured for fluid communication with the second reservoir andthe user.
 17. The fluid delivery device of claim 12, wherein the deviceis an ambulatory infusion pump.
 18. The fluid delivery device of claim13, wherein the bolus drive mechanism includes a ratchet and piston. 19.The fluid delivery device of claim 13, wherein the bolus of the firstmedicament is larger than the bolus of the second medicament.